ES2329374T3 - Formulaciones farmaceuticas que utilizan esfingolipidos de cadena corta y usos de las mismas. - Google Patents

Formulaciones farmaceuticas que utilizan esfingolipidos de cadena corta y usos de las mismas. Download PDF

Info

Publication number: ES2329374T3
Authority: ES; Spain
Prior art keywords: independently; pharmaceutical formulation; formulation according; drug; doxorubicin
Prior art date: 2003-11-14
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

ES04798989T

Other languages

English (en)

Spanish (es)

Inventor

Robert Jan Veldman

Wim J. Van Blitterswijk

Marcel Verheij

Gerben A. Koning

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

HET NL KANKER I NETHERLAND

HET NEDERLANDS KANKER INSTITUUT (THE NETHERLANDS CANCER INSTITUTE)

Original Assignee

HET NL KANKER I NETHERLAND

HET NEDERLANDS KANKER INSTITUUT (THE NETHERLANDS CANCER INSTITUTE)

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2003-11-14

Filing date

2004-11-11

Publication date

2009-11-25

2003-11-14 Priority claimed from GB0326642A external-priority patent/GB0326642D0/en

2003-11-17 Priority claimed from GB0326759A external-priority patent/GB0326759D0/en

2004-11-11 Application filed by HET NL KANKER I NETHERLAND, HET NEDERLANDS KANKER INSTITUUT (THE NETHERLANDS CANCER INSTITUTE) filed Critical HET NL KANKER I NETHERLAND

2009-11-25 Application granted granted Critical

2009-11-25 Publication of ES2329374T3 publication Critical patent/ES2329374T3/es

2024-11-11 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

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Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Epidemiology (AREA)
Dispersion Chemistry (AREA)
Dermatology (AREA)
Molecular Biology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicinal Preparation (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

ES04798989T 2003-11-14 2004-11-11 Formulaciones farmaceuticas que utilizan esfingolipidos de cadena corta y usos de las mismas. Expired - Lifetime ES2329374T3 (es)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB0326642		2003-11-14
GB0326642A GB0326642D0 (en)	2003-11-14	2003-11-14	Pharmaceutical formulations
GB0326759A GB0326759D0 (en)	2003-11-17	2003-11-17	Pharmaceutical formulations and their preparation and use
GB0326759		2003-11-17

Publications (1)

Publication Number	Publication Date
ES2329374T3 true ES2329374T3 (es)	2009-11-25

Family

ID=34593738

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES04798989T Expired - Lifetime ES2329374T3 (es)	2003-11-14	2004-11-11	Formulaciones farmaceuticas que utilizan esfingolipidos de cadena corta y usos de las mismas.

Country Status (6)

Country	Link
US (2)	US7915227B2 (fr)
EP (1)	EP1686959B1 (fr)
AT (1)	ATE434431T1 (fr)
DE (1)	DE602004021713D1 (fr)
ES (1)	ES2329374T3 (fr)
WO (1)	WO2005046637A2 (fr)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2329374T3 (es) *	2003-11-14	2009-11-25	Het Nederlands Kanker Instituut (The Netherlands Cancer Institute)	Formulaciones farmaceuticas que utilizan esfingolipidos de cadena corta y usos de las mismas.
AU2005303389A1 (en) *	2004-11-15	2006-05-18	Yissum Research Development Company Of The Hebrew University Of Jerusalem	Combination therapy associating preferably a ceramide with a cytotoxic drug
US7727537B2 (en)	2005-02-14	2010-06-01	Dpm Therapeutics Corp.	Stabilized compositions for topical administration and methods of making same
DK1853303T3 (en) *	2005-02-14	2016-02-29	Dpm Therapeutics Corp	STABILIZED COMPOSITIONS FOR TOPIC ADMINISTRATION AND PROCEDURES FOR PREPARING IT
US7838011B2 (en)	2005-02-14	2010-11-23	Pankaj Modi	Stabilized protein compositions for topical administration and methods of making same
WO2008005824A1 (fr)	2006-06-30	2008-01-10	The Scripps Research Institute	Adjuvants et procédés d'utilisation
CN106310293A (zh)	2007-09-27	2017-01-11	免疫疫苗技术有限公司	在包括连续疏水相的载体中的脂质体在体内输送多核苷酸中的应用
US20100209452A1 (en) *	2007-10-03	2010-08-19	Immunovaccine Technologies, Inc	Compositions comprising an antigen, an amphipathic compound and a hydrophobic carrier, and uses thereof
CN101244038B (zh) *	2007-10-26	2010-12-08	吴念	稳定型阿霉素类脂质体及其制备方法
CA2723918C (fr)	2008-06-05	2018-01-09	Immunovaccine Technologies Inc.	Compositions contenant des liposomes, un antigene, un polynucleotide et un transporteur comprenant une phase continue d'une substance hydrophobe
AR093275A1 (es) *	2010-03-17	2015-05-27	Centro De Excelencia En Productos Y Procesos De Cordoba (Ceprocor)	Una composicion farmaceutica soluble en agua que comprende al menos una sustancia terapeuticamente activa de caracteristicas hidrofobicas y al menos un compuesto seleccionado entre los sialoglicoesfingolipidos, los glicoesfingolipidos o una mezcla de sialoglicoesfingolipidos y glicoesfingolipidos
US10105435B2 (en)	2011-10-06	2018-10-23	Immunovaccine Technologies Inc.	Liposome compositions comprising an adjuvant that activates or increases the activity of TLR2 and uses thereof
WO2014144365A1 (fr) *	2013-03-15	2014-09-18	University Of Maryland, College Park	Formulations nano-liposomiques et procédés d'utilisation
WO2016049250A1 (fr) *	2014-09-24	2016-03-31	The Board Of Trustees Of The University Of Illinois	Plaquettes artificielles pour le traitement du saignement catastrophique
WO2018146506A1 (fr) *	2017-02-10	2018-08-16	Universitat Politècnica De València	Dérivés thérapeutiques

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4416872A (en) *	1982-03-17	1983-11-22	The United States Of America As Represented By The Secretary Of The Army	Treatment of malaria with liposomes containing 8-aminoquinoline derivatives and glycoconjugates
GB8620361D0 (en)	1986-08-21	1986-10-01	Windleshaw Enterprises Ltd	Pharmaceutical compositions
US5527528A (en) *	1989-10-20	1996-06-18	Sequus Pharmaceuticals, Inc.	Solid-tumor treatment method
US5013556A (en) *	1989-10-20	1991-05-07	Liposome Technology, Inc.	Liposomes with enhanced circulation time
US5936076A (en) *	1991-08-29	1999-08-10	Kirin Beer Kabushiki Kaisha	αgalactosylceramide derivatives
US5395619A (en) *	1993-03-03	1995-03-07	Liposome Technology, Inc.	Lipid-polymer conjugates and liposomes
JP3499604B2 (ja)	1994-07-25	2004-02-23	財団法人神奈川科学技術アカデミー	スフィンゴ糖脂質ミセルからなる薬物担体
US6054433A (en) *	1994-11-03	2000-04-25	The Regents Of The University Of California	Methods and compositions for stimulating tissue growth and epithelial moisturization
US5800833A (en) *	1995-02-27	1998-09-01	University Of British Columbia	Method for loading lipid vesicles
WO1997030696A1 (fr)	1996-02-26	1997-08-28	Daiichi Pharmaceutical Co., Ltd.	Liposome et dispersion de liposome
DE69943314D1 (de) *	1998-02-12	2011-05-12	Kapil N Bhalla	Sphingolipid-derivate und verfahren zu deren verwendung
WO2002002078A2 (fr) *	2000-06-30	2002-01-10	Inex Pharmaceuticals Corporation	Améliorations apportées à des encapsulations de camptothécines dans des liposomes et applications
ES2329374T3 (es) *	2003-11-14	2009-11-25	Het Nederlands Kanker Instituut (The Netherlands Cancer Institute)	Formulaciones farmaceuticas que utilizan esfingolipidos de cadena corta y usos de las mismas.

2004
- 2004-11-11 ES ES04798989T patent/ES2329374T3/es not_active Expired - Lifetime
- 2004-11-11 EP EP04798989A patent/EP1686959B1/fr not_active Expired - Lifetime
- 2004-11-11 AT AT04798989T patent/ATE434431T1/de not_active IP Right Cessation
- 2004-11-11 DE DE602004021713T patent/DE602004021713D1/de not_active Expired - Lifetime
- 2004-11-11 US US10/579,230 patent/US7915227B2/en not_active Expired - Fee Related
- 2004-11-11 WO PCT/IB2004/003886 patent/WO2005046637A2/fr not_active Ceased
2011
- 2011-03-02 US US13/038,655 patent/US20110150984A1/en not_active Abandoned

Also Published As

Publication number	Publication date
WO2005046637A2 (fr)	2005-05-26
US20110150984A1 (en)	2011-06-23
US7915227B2 (en)	2011-03-29
WO2005046637A3 (fr)	2005-07-07
EP1686959B1 (fr)	2009-06-24
US20070082855A1 (en)	2007-04-12
ATE434431T1 (de)	2009-07-15
DE602004021713D1 (de)	2009-08-06
EP1686959A2 (fr)	2006-08-09

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ES2272280T3 (es)	2007-05-01	Conjugado que presenta un enlace escindible para uso en un lipososma.
CA1237670A (fr)	1988-06-07	Reduction de la toxicite de certains medicaments
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JP2004525138A (ja)	2004-08-19	治療剤の改良された細胞内送達のためのリポソーム組成物
PT785773E (pt)	2001-05-31	Lipossomas de eteres lipidicos e sua utilizacao terapeutica
US20190328665A1 (en)	2019-10-31	Liposome compositions encapsulating modified cyclodextrin complexes and uses thereof
CN103957912A (zh)	2014-07-30	疏水性喜树碱衍生物的药物组合物
EP2384743A1 (fr)	2011-11-09	Formulation siosomal pour l'administration intracellulaire et le ciblage des agents thérapeutiques
JP6744046B2 (ja)	2020-08-19	ｃＧＭＰアナログの標的化されたリポソーム送達
US10617672B2 (en)	2020-04-14	Liposome composition co-encapsulating doxorubicin and a prodrug of mitomycin C
Veldman et al.	2005	Coformulated N-octanoyl-glucosylceramide improves cellular delivery and cytotoxicity of liposomal doxorubicin
ES2380620T3 (es)	2012-05-16	Tratamiento de tumores resistentes a múltiples fármacos mediante un conjugado de mitomicina C
US20250064784A1 (en)	2025-02-27	Liposome composition comprising liposomal prodrug of mitomycin c and methods of treatment
ES2283423T3 (es)	2007-11-01	Emulsion estructurada de anfotericina b.
WO2005123078A1 (fr)	2005-12-29	Préparation de liposome contenant du camptothecin legérement soluble dans l'eau
Messerer	2002	Liposomal encapsulation of irinotecan and potential for the use of liposomal drug in the treatment of liver metastases associated with advanced colorectal cancer
Wang et al.	2024	Improved Antitumor Efficiency of N4-Tetradecyloxycarbonyl Gemcitabine-Loaded Liposomes for Pancreatic Cancer Chemotherapy
WO2025184543A1 (fr)	2025-09-04	Compositions et méthodes d'administration de composés thérapeutiques
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PL197938B1 (pl)	2008-05-30	Liposomowy preparat zawierający przeciwnowotworową substancję aktywną, sposób jego wytwarzania i zawierająca go kompozycja farmaceutyczna